title: Sall3 plays essential roles in horizontal cell maturation through regulation of neurofilament expression levels.
abstract: The region-specific homeotic gene spalt (sal) gene plays a critical role in Drosophila development. The mammalian Sal homologous genes contain four members, and Sall3 is mainly expressed in horizontal cells. In the developing retinas of Sall3 knockout (KO) mice until around birth, horizontal precursor cells developed with comparable numbers and position; the horizontal cell marker NF160 was expressed weakly and neurite-like structure had once formed. Since Sall3-KO mice die at postnatal day 1, subsequent retinal development was examined by in vitro retinal explant culture. In the Sall3-KO retina culture, the expression of NF160 was abrogated, and neurite extension was not observed. Furthermore, Sall3-KO horizontal precursors were initially localized at the appropriate horizontal positions, but eventually moved to an abnormal site in the outer nuclear layer. Overexpression of Sall3 in retinal progenitors did not induce differentiation of retinal progenitor cells into the horizontal cell-fate, but enhanced NF160 expression and neurite extension. In addition, differentiation into Müller glia was promoted, and rod cells were severely suppressed without perturbing proliferation. In conclusion, Sall3 may not be involved in horizontal cell-fate determination, but rather functions to instruct terminal differentiation of horizontal cells and to maintain NF160 expression.
authors.affiliation: Department of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Baba
authors.forename: Atsumi
authors.initials: A
authors.lastname: Iida
authors.forename: Sumiko
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D064026:Calbindins; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism; D017353:Gene Deletion; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D016501:Neurites / Q000378:metabolism; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051248:Retinal Horizontal Cells / Q000166:cytology / Q000378:metabolism*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D046509:Tissue Culture Techniques; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D064026:Calbindins; D017630:Connexins; D005136:Eye Proteins; C119811:Gja10 protein, mouse; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C499523:Lhx1 protein, mouse; D016900:Neurofilament Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D064030:S100 Calcium Binding Protein G; C484467:Sall3 protein, mouse; D014157:Transcription Factors; C044882:neurofilament protein L; C061195:neurofilament protein M; D053148:Caspase 3